PB2282: MEK-KINASE INHIBITOR (TRAMETINIB) AS A TREATMENT OPTION FOR HAIRY CELL LEUKEMIA
Authors: Svetlana Smirnova, Lyubov Al-Radi, Tatyana Moiseeva, Margaritta Gurjanova, Igor Yakutik, Andrey Sudarikov, Valentina Dvirnik, Alla Kovrigina
Journal: HemaSphere (2023)

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Hairy cell leukemia (HCL) is a chronic indolent B–cell lymphoproliferative disease with good respose to therapy in the majority if the cases. However, despite the successes achieved in treatment, there is a group of patients with a resistant/recurrent course of the disease, a short remission after the main course or contraindications to the standard treatment. Since the discovery of a marker mutation of the BRAFV600E gene and constitutive activation of the RAS-RAF-MEK-ERK pathway, the therapeutic inhibitors of this pathway have been of particular interest in the treatment of complicated cases of HCL. The literary data on the use of monotherapy with the MEK kinase inhibitor trametinib are quiet insufficient. Aims: Description of clinical cases of the use of trametinib monotherapy in HCL Methods: Monotherapy by Trametinib was applied in 3 patient with classic HCL. The diagnosis of HCL was established according to the WHO classification criteria, including immunophenotiping of lymphocytes, morphological and immunohistochemistry of bone marrow, BRAFV600E mutation. Trametinib was used in a dose of 1mg/day. In 2 patients, Trametinib was used for 2 months, in 1 patient for 16 months and the therapy with trametinib continues at the same dose. Results: We present our experience of 3 clinical cases of the use of trametinib in the treatment of HCL. Two cases were BRAFV600Eneg, nevertheless had classical HCL immunophenotype of lymphocytes, one case was classic BRAFV600Epos HCL. The use of standard therapy in two clinical cases was not impossible due the deep neutropenia and severe infectious complications at the diagnosis or due to the absense of BRAFV600E mutation. So trametinib was used as the preliminary stage in a dose of 1mg/day for 2 months before the main course of purine analogs. After 2 months was observed an increase of absolute neutrophil count and resolution of the infectious complications, which allowed applying cladribine therapy. After 1 standard course (0.1 mg/kg/day x 7 days) of cladribine chemotherapy both patients achieved complete clinical remission. In one case with a resistant/relapsing course of BRAFV600Eneg HCL (after 6 therapy lynes: splenectomy, IF-α + cladribine, 2 courses of cladribine with rituximab and with obinutuzumab, anti-CD22 immunotoxin moxetumomab pasudotox), trametinib monotherapy was started and allowed to achieve a good partial remission. Therapy is still continues without the decrease in the quality of life. Summary/Conclusion: Trametinib can be used as a preliminary stage in patients with HCL without BRAF mutation and as the main antitumor therapy in patients with resistant/recurrent HCL. At the same time, the drug is effective in the absence of the MAP2K1 mutation (unlike vemurafenib, which effective only in the presence of the BRAFV600E mutation), and, like vemurafenib, trametinib monotherapy can be effective at a reduced dose (1 mg/day or 1 mg every other day). Keywords: Kinase inhibitor, Treatment, MEK, Hairy cell leukemia